Charged grafts and methods for using them

ABSTRACT

A system for preventing thrombosis in an implantable medical device includes an implantable medical device sized for implantation at least partially within a patient&#39;s body. The device includes an at least partially electrically conductive portion that is disposed within a patient&#39;s body upon implantation, an electrode coupled to the electrically conductive portion of the device; and a power source coupled to the electrode. The power source provides a negative electric charge to the at least partially electrically conductive portion for an indefinite period of time. The device may be configured to resist thrombosis, infection, and/or undesired tissue growth via the charged conductive portion once implanted. Exemplary embodiments of the implantable medical device include a hemodialysis vasculature graft, a dialysis catheter, a coronary artery, and a heart valve.

RELATED APPLICATION DATA

This application is a continuation of co-pending application Ser. No.13/431,933, filed Mar. 27, 2012, and issuing as U.S. Pat. No.10,835,646, which is a continuation of International Application No.PCT/US2010/050419, filed Sep. 27, 2010, which claims benefit ofprovisional application Ser. No. 61/246,457, filed Sep. 28, 2009, theentire disclosures of which are expressly incorporated by referenceherein.

FIELD OF THE INVENTION

The present invention relates generally to devices that may be implantedwithin a patient's body, and, more particularly, to electrically chargedimplants, e.g., which may reduce susceptibility to infection,thrombosis, and/or undesired tissue growth, and to apparatus and methodsfor making and using them.

BACKGROUND

Two common problems with implanted devices are infection and thrombosis.Microbes adhere to foreign material and often form a biofilm. Thisbiofilm is relatively resistant to attack by immune molecules and cells,and also relatively impermeable to therapeutic levels of antibiotics andother drugs. Accordingly, an implant, whether it is a simple intravenouscatheter, a heart valve, a vascular graft, or a total hip prosthesis,once infected, often must be removed to achieve clearance of theinfection. The device, if still needed, is then replaced after theinfection is cleared.

In addition, another shortcoming of many prosthetic vascular graftmaterial, valves, and catheters is the propensity of blood to clot whenin contact with foreign material. Depending on the location andcriticality of the application, various solutions have been proposed tolimit such clotting. In the setting of a mechanical heart valve, forexample, systemic blood thinners (e.g., Coumadin or Warfarin) may begiven orally to reduce the propensity of clot formation. Such compoundsmust usually be converted to a shorter-acting injectable drug if apatient is to undergo any invasive procedure. This is generallyeffective, though with an associated risk of bleeding from what mayotherwise be a minor injury. This risk of bleeding, particularlyintracranial bleeding, is increased in the elderly who are unfortunatelythe most likely patients to have an artificial valve or other medicalimplant.

Catheters, such as for hemodialysis, may be filled with a concentratedsolution of heparin in saline. While large diameter vascular graftstypically do not suffer from thrombosis, small diameter grafts may bedoomed to failure, in part due to thrombosis for which no othereffective, safe prevention has been identified. This has prevented theavailability of a prosthetic coronary artery graft, and frequently doomsgrafts in the lower leg to failure.

Accordingly, apparatus and methods that may reduce susceptibility toinfection, thrombosis, and/or undesired tissue growth often associatedwith temporarily or permanently implanted devices would be useful.

SUMMARY OF THE INVENTION

The present invention is directed to implantable medical devices, e.g.,for reducing and/or preventing thrombosis, infection, and/or undesiredtissue growth, and to apparatus and methods for making and using them.For example, the apparatus and methods described herein may limit theability of microbes to adhere to prosthetic material, e.g., to vasculargrafts, valves, and catheters of any type, but may be applicable toalmost any medical implant.

The apparatus and methods described herein may be applied to variousdevices that may be implanted temporarily or substantially permanentlywithin a patient's body, for example, devices in the fields of vascularsurgery and/or cardiac surgery, such as vascular grafts, mechanicalheart valves, and intravenous or intra-arterial catheters. Suchcatheters may be intended to remain in place within a patient's body foran extended period of time, for example, dialysis catheters in anyanatomic position, peritoneal dialysis catheters, and/or single ormultiple lumen catheters, which may be placed in critically illpatients. Such catheters are often referred to by their anatomiclocations, e.g., a “subclavian line,” “femoral line,” and the like.

Most cells have a negative charge on their surface, largely carried byprotein and carbohydrate molecules on their surface, collectivelysometimes referred to as known as glycocalyx. This is true of red bloodcells and platelets, as well as endothelial cells. These negativelycharged surfaces reduce the interactions between cells and the vascularwalls and contribute to the absence of thrombosis in anatomic vessels.When the endothelium is injured, however, the basement membrane may beexposed, thus attracting and helping to activate platelets. Apparatusand methods described herein may involve applying a slight negativecharge to medical implants, e.g., to reduce interaction with negativelycharged cells within the body, and to inhibit the intrinsic or extrinsicpathways of the coagulation cascade, for example, to reduce thrombosis,infection, and/or undesired tissue growth.

In accordance with one embodiment, a system is provided for preventingthrombosis in an implantable medical device. The system generallyincludes an implantable medical device sized for implantation at leastpartially within a patient's body, the device including an at leastpartially electrically conductive portion that is exposed within apatient's body upon implantation. For example, the at least partiallyconductive portion may include an electrically semi-conductive material,or an electrically conductive material covered with a thin layer ofsemi-conductive or non-conductive material, to limit or otherwisecontrol leakage or other electrical flow from and/or through theconductive portion.

A power source may be coupled to the at least partially conductiveportion of the device, e.g., via one or more electrodes, for providing anegative electric charge to the at least partially electricallyconductive portion, e.g., for maintaining a slight negative electriccharge between about 0 and 0.5 Volts (0−0.5 V) on the at least partiallyconductive portion. The power source may include a circuit, e.g., aninverting operational amplifier or a voltage divider, coupled to abattery and/or other electrical storage device for providing thenegative charge to the at least partially conductive portion. Inexemplary embodiments, the device may be a heart valve, a vasculargraft, a catheter, an aortic endograft, or other implantable device.

In accordance with another embodiment, a method is provided forpreventing thrombosis, infection, and/or undesired tissue growth on animplantable device that includes implanting the device within apatient's body, the device including an at least partially electricallyconductive portion. A negative electrical charge is applied to and/ormaintained on the conductive portion for an indefinite time, e.g., toprevent cells from adhering to the conductive portion and/or inhibit atleast partially the intrinsic and or extrinsic coagulation pathways.

In another embodiment, a urinary bladder catheter may be constructedsuch that at least a portion of the surface of the catheter iselectrically conductive. A power source is connected to the cathetersuch that the surface of the catheter is electrically charged at leastpart of the time the catheter is placed in the bladder. By providing anelectrical charge on the surface of at least a portion of the catheter,urinary tract infection may be prevented.

Similarly, conductive and charged surfaces may be provided on cathetersfor peritoneal dialysis catheters. In another embodiment, a nephrostomytube is constructed with at least a portion of the surface electricallyconductive. A power supply is provided to maintain an electrical chargeon at least a portion of the catheter.

In yet another embodiment, a central venous catheter is constructed withan electrically conductive surface over at least a portion of thecatheter. A source of electrical energy, for example a battery or otherpower supply, and a lead connecting the battery to the catheter are alsoprovided. A skin electrode connects the circuit from the patient's skin,through the battery, to the lead, and the catheter, which then completesthe circuit within the patient.

In accordance with still another embodiment, a fluid conduit is providedthat includes a surface, at least a portion of the surface beingelectrically conductive. Means for applying an electrical charge to theconductive surface may also be provided, e.g., a battery or other powersource, coupled to the electrically conductive surface. At least aportion of the conduit may be sized for at least temporary implantationinto a human patient. As used herein, “fluid conduit” refers to anytubular device, graft, and the like that may be implanted or otherwiseintroduced into a patient's body, e.g., catheters or grafts for dialysisaccess, peritoneal dialysis access, Foley catheters, nephrostomy tubes,endotracheal tubes, nasogastric tubes, and the like. The fluid conduitmay be sized for introduction into an existing or created body lumen,e.g., within a patient's urinary tract, cardiovascular system, biliarysystem, and the like, and may include a lumen for conducting fluidtherealong, e.g., urine, blood, bile, normal saline, lactated ringer'ssolution, and the like.

Other aspects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate exemplary embodiments of the invention, inwhich:

FIG. 1A is a perspective view of a first embodiment of an implantablemedical device, including a vascular graft and a power source coupled toa portion of the graft.

FIG. 1B is a cross-sectional view of the graft of FIG. 1A, taken alongline 1B-1B.

FIG. 2 is a perspective view of another embodiment of an implantablemedical device, including a heart valve assembly and a power sourcecoupled to a portion of the heart valve assembly.

FIGS. 3A and 3B are perspective and cross-sectional views, respectively,of yet another embodiment of an implantable medical device, including anarteriovenous hemodialysis access graft and a power source coupled to aportion of the access graft.

FIGS. 4A and 4B are perspective and cross-sectional views, respectively,of still another embodiment of an implantable medical device, includingan implantable blind-ended tubular graft and a power source coupled to aportion of the graft.

FIG. 4C is a partial cross-sectional view of a body, showing a pair ofimplanted blind-ended tubular grafts, such as that shown in FIGS. 4A-4B,implanted within the body.

FIG. 5 is a partial cross-sectional view of a body, showing anotherembodiment of an implanted medical device, including a dialysis catheterand a power source, implanted within the body.

FIG. 6 is a cross-sectional view of a body, showing yet anotherembodiment of an implantable medical device, including an endovascularaortic aneurysm repair graft and a power source, implanted within thebody.

FIG. 7 is a flowchart showing an exemplary method for implanting amedical device for preventing thrombosis on the implantable device.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Turning to the drawings, FIGS. 1A-1B show an exemplary embodiment of amedical device 10 that may be implanted within a body, e.g., forresisting thrombosis, infection and/or undesired tissue growth. Asshown, the device 10 generally includes an elongate tubular member 12and a power or voltage source 14, and may be suitable as a vasculargraft, e.g., to provide a prosthetic coronary artery bypass graftconnected between other vessels or body lumens, to replace a segment ofa vessel or body lumen, or to be implanted within a vessel or body lumen(not shown).

Generally, the tubular member 20 includes a proximal end 22, a distalend 24, and a lumen 26 defined by an inner surface 28 extending betweenthe proximal and distal ends 22, 24. In exemplary embodiments, thetubular member 20 may have a diameter or other cross-section betweenabout one and six millimeters (1-6 mm), and a length between about fiftyand five hundred millimeters (50-500 mm). At least a portion of thetubular member 20 is at least partially electrically conductive, e.g.,for maintaining an electrical charge on at least the portion for anextended period of time, as described further below.

For example, as best seen in FIG. 1B, the tubular member 20 may includeone or more layers, e.g., a base layer 32 and an at least partiallyconductive layer 34. The base layer 32 may be formed from fabric orother woven tubular material, such as Dacron, a polymeric or otherplastic tube, such as expanded PTFE, or other material, similar toconventional grafts. Optionally, the proximal and/or distal ends 22, 24may include one or more features, e.g., connectors and the like (notshown) for facilitating implantation of the tubular member 20. Forexample, the proximal and/or distal ends 22, 24 may include connectors(not shown) for creating an anastomosis between the ends 22, 24 andother body lumens, stents (also not shown) for securing the ends 22, 24within a body lumen, and the like.

Unlike conventional grafts, the tubular member 20 includes an at leastpartially conductive layer 34, which in the embodiment shown in FIGS. 1Aand 1B is disposed on an interior of the tubular member 20, i.e.,exposed along the lumen 26. The conductive layer 34 may extend along theentire length of the tubular member 20 or may be provided only at theproximal and/or distal ends 22, 24, depending upon the application. Inaddition or alternatively, the tubular member 20 may include an outerlayer and/or an intermediate layer of an at least partially conductivematerial (not shown), similar to the conductive layer 34, as describedfurther elsewhere herein.

The conductive layer 34 may be composed of any of one or moreelectrically conductive or semi-conductive materials. The conductivelayer 34 may be bonded to or otherwise coated onto the base layer 32,i.e., within the lumen 26 of the tubular member 20. Alternatively, theconductive layer 34 may be applied to a mandrel, e.g., a rod or tubehaving a desired diameter for the lumen 26, and the base layer 32 may beapplied around or otherwise over the conductive layer 34. Once the baselayer 32 and conductive layer 34 are bonded or otherwise fixed to oneanother, the mandrel may be removed.

Optionally, other features may be applied to the structure before orafter removal from the mandrel, e.g., connectors, electrodes, and thelike, as described elsewhere herein. For example, one or more electrodesmay be bonded or otherwise coupled to the conductive layer 34 eitherbefore or after applying the base layer 32 over the conductive layer 34.

The conductive layer 34 may be semi-conductive, i.e., may havesufficient resistance to prevent substantial current flow along and/orfrom the conductive layer, thereby maintaining a desired electricalcharge, e.g., a slight negative charge, along the lumen 26 of thetubular member 20. In addition or alternatively, the conductive layer 34may maintain a desired electrical charge just beneath one or moreexposed surfaces of the tubular member 12, e.g., to act similar to acapacitor in maintaining a charge for an extended period of time withoutsubstantial current flow or leakage.

For example, the conductive layer 34 may be semi-conductive such thatcurrent “leaks” from the conductive layer 34, i.e., flows at asubstantially slow rate, thereby maintaining a desired voltage on theinner surface 28 with minimal current and power consumption. In oneexemplary embodiment, the conductive layer 34 may be a conductivepolymer, such as Poly(3,4-Ethylenedioxythiophene)/poly(styrenesulfonate), e.g., having athickness between about a few microns. In another exemplary embodiment,the conductive layer 34 may include a relatively thin layer of asilicone dispersion loaded with conductive particles (not shown). Forexample, the conductive particles may be silver particles, silver coatedglass beads, or platinum coated carbon particles, e.g., between aboutone and seven microns (0.001-0.007 inch or 0.025-0.175 mm) in averagediameter.

In an alternative embodiment, an additional electrically insulatingcoating or layer (not shown) may be provided over the conductive layer34. For example, the inner surface of the lumen 26 (and optionally theends 22, 24) may be coated with a polymer or material that is notelectrically conductive, such as silicone, polyurethane, orfluoropolymer, thereby limiting the conductivity of the entire innersurface and/or the most proximal and distal portions of the innersurface. The coating may be relatively thin, e.g., having a thicknessbetween about 0.0001 and 0.1 millimeter (0.0001-0.1 mm), therebyreducing the conductivity while still allowing an electrical charge tobe maintained on the desired portion(s) of the inner surface. In thisalternative, more conductive materials may be used for the conductivelayer 34, and the coating thickness may be adjusted to provide thedesired level of conductivity.

In an alternative embodiment, the tubular member 20 may be formed frompolymeric, plastic, or other base material including one or moreconductive particles, such as carbon or those identified elsewhereherein, dispersed within the material. For example, the tubular member20 may be formed from polyurethane, silicone rubber, or othernon-electrically conductive material loaded with conductive particles.For example, a mixture of the desired base material and the conductiveparticles may be provided within an extruder, and the mixture may beextruded substantially continuously into a tubular shape, which may becut or otherwise separated into one or more tubular members 20.Alternatively, the mixture may be placed within a mold, cast, or otherdevice for forming the mixture into the tubular member 20.

In this alternative, one or more portions of the tubular member 20 maybe coated with an electrically insulating layer, e.g., similar to theinsulating layers described elsewhere herein. For example, the outersurface and/or end surfaces of the tubular member 20 may be coated,e.g., to prevent electrical leakage from these surfaces and/or to applythe desired charge only to the inner surface 28.

In addition, as shown in FIG. 1A, one or more electrodes 16 may beprovided on the tubular member 20. For example, as shown, an electrode16 may be provided on each of the proximal and distal ends 22, 24 of thetubular member 20. The electrodes 16 may extend transversely from thetubular member 20, e.g., through the base layer 32 to electricallycouple the electrodes 16 to respective ends of the conductive layer 34.Alternatively, the electrodes 16 may be conductive regions (not shown)applied or otherwise formed on the exterior of the proximal and distalends 22, 24, e.g., for endoluminal applications.

The electrodes 16 may be coated, covered, or otherwise electricallyinsulated to prevent current flow, e.g., from the electrodes 16 totissue, fluid, or other areas adjacent the electrodes 16 and/or outsidethe tubular member 20. One or more wires or other electrical leads 18may be coupled to the electrodes 16, e.g., by soldering, bonding,fusing, and the like, which may extend from the tubular member 12, e.g.,to the power source 14. Alternatively, the leads 18 may be formed fromsilicone integrated with silver particles, similar to other materialdescribed herein. In another alternative, the leads 18 may be formedfrom a conductive epoxy, such as CW2400 (Chemtronics®).

Optionally, the leads 18 may be coupled directly to the conductiveportion 34 of the tubular member 20, e.g., through the base layer 32.The leads 18 may be simply insulated electrical wires compatible withbeing implanted within a patient's body, e.g., to extend along one ormore body lumens, through body cavities, and/or tissue, as describedelsewhere herein.

With continued reference to FIG. 1A, the power source 14 generallyincludes a circuit 50 and a battery or other storage device 52, e.g.,provided within a casing 54. The casing 54 may have a size and/or shapeto facilitate implantation within a patient's body, e.g., subcutaneouslyor deep within the body, as described further elsewhere herein.

The battery 52 may be a single use device, e.g., that may be replacedafter being depleted, or may be rechargeable, e.g., using a source (notshown) outside a patient's body. In an exemplary embodiment, the battery52 may be a direct current (DC) voltage source. The circuit 50 may beany number of resistive or active elements to control the flow ofelectrical current from the battery 52, e.g., to the tubular member 12.In exemplary embodiments, the circuit 50 may be an inverting operationalamplifier or a simple voltage divider circuit. In yet anotherembodiment, the power source 14 may simply include a battery, and thecircuit 50 may be omitted. Additionally, the circuit may include thebattery in series with a resistor also in series with the conductivesurface of the device, which is then in series through the tissues ofthe patient, completing the circuit back to the battery.

Optionally, the power source 14 may include a switch (not shown) foractivating and/or deactivating the power source 14. For example, if thepower source 14 is implanted subcutaneously beneath a patient's skin, aswitch may be provided on the casing 54 that may be selectively actuatedby pressing on the skin above the casing 54. In addition oralternatively, the power source 14 may include a telemetry device, e.g.,a transmitter and/or receiver, for communicating to locations externalto the patient's body. For example, the telemetry device may include aradio frequency, acoustic, inductive, or other transceiver that maycommunicate through intervening tissue within an external device. Such atelemetry device may be used to activate and/or deactivate the powersource 14, to recharge the battery 50, and/or for other communications,as is known in the art.

The power source 14 may be implanted in relatively close proximity tothe tubular member 12, e.g., within a body lumen or cavity adjacent thetubular member 12. Optionally, the power source 14 may be mounteddirectly on or to the tubular member 12. Alternatively, the power source14 may be implanted remotely from the tubular member 12, e.g.,subcutaneously, and the lead(s) 18 may extend between the power source14 and the tubular member 12.

The power source 14 may be electrically coupled to the tubular member12, e.g., via leads 18, such that a negative charge is imparted to theconductive layer 34. The imparted negative charge may repel negativelycharged blood cells and/or other cells, and or may inhibit the intrinsicand or extrinsic pathways of the clotting cascade e.g., to reduce therisk of thrombosis, infection, or undesired tissue growth within thelumen 26 of the tubular member 12. In addition or alternatively, thepower source 14 may be configured to impart a negative charge to anotherconductive layer (not shown), e.g., on or adjacent the outer surface ofthe tubular member 12. The power source 14 may be configured tosimultaneously, alternatively, or separately impart a negative charge tothe conductive layer 34 and other conductive layer(s). In yet anotherembodiment, the power source 14 may be coupled to the tubular member 12such that a negative charge is imparted to the conductive layer 34,while a positive charge is imparted to another conductive layer (notshown), e.g., on the outer surface of the tubular member 12.

Alternatively, the power source 14 may be electrically coupledindirectly to the tubular member 12. For example, one lead 18 may extendfrom the power source 14 to the tubular member 12 and the other lead 18may be coupled to an anatomical structure adjacent to the tubular member12 or otherwise within the patient's body such that the anatomicalstructure (and any intervening structures, fluids, and then like)provides a conductive path to complete the circuit between the powersource 14 and the tubular member 12. Alternatively, at least a portionof the casing 54 may be coupled to the positive terminal of the battery50 to provide a positive charge on the casing 54, which may create acircuit partially through the patient's body with the negatively chargedportion of the tubular member 12. The tubular member 12 may be coupledto the negative terminal of the battery 50, e.g., by a single lead 18.

Turning to FIG. 2, another embodiment of an implantable medical assembly100 is shown that includes a mechanical heart valve 112 and a powersource 14, which may be similar to the embodiments described above.Generally, the heart valve 112 includes a frame 128, e.g., having acircular or other annular shape and one or more valve elements 130connected to the frame 128 such that the valve elements 130 may open andclose, similar to conventional heart valves.

The components of the heart valve 112 may be formed from conventionalmaterials, e.g., such as pyrolytic carbon, or conductive orsemi-conductive materials, similar to other embodiments describedherein. In one embodiment, the frame 128 and valve elements 130 of theheart valve 112 may be formed a rigid or semi-rigid material, such aspyrolytic carbon. Unlike conventional valves, one or more outer surfacesof the valve elements 130 and/or other surfaces of the heart valve 112,e.g., that may be exposed to blood flow, may be coated with an at leastpartially conductive layer (not shown), such as those describedelsewhere herein. For example, the conductive layer may be bonded to orotherwise cover the valve elements 130 to provide a desired voltageand/or current leakage from the valve elements 130.

In an exemplary embodiment, the conductive layer may include a polymer,such as Poly(3,4-Ethylenedioxythiophene)/poly(styrenesulfonate), or amonomer, such as 3,4-Ethylenedioxythiophene, which may be polymerized byadding Ferric Toluene Sulfonate as an oxidant. In yet anotherembodiment, the valve elements 130 may be coated with a polymer loadedwith conductive particles, such as silver particles as describedelsewhere herein. Alternatively, the valve elements 130 may be formedfrom electrically conductive material, such as stainless steel. In thisalternative, the valve elements may be coated with a polymer or othermaterial to reduce the conductivity of the material, similar to otherembodiments described elsewhere herein.

One or more electrodes 116 may be coupled to a portion of the heartvalve 112, e.g., to the frame 128 and/or valve elements 130, and thepower source 14 may be coupled to the heart valve 112 via one or moreleads 118. For example, as shown in FIG. 2, an electrode 116 is coupledto the valve elements 130 (e.g., to the semi-conductive coating and/orunderlying conductive material), and an electrical lead 118 extends fromthe electrode 116 to the power source 14. The power source 14 may besimilar to the previous embodiments, e.g., configured to impart anegative charge to the valve elements 130. For example, the lead 118 amay be coupled to the negative terminal of the battery 50, and anotherlead 118 b may extend from the power source 14, e.g., coupled to thepositive terminal of the battery 50, to an electric pad 123, which maybe coupled to an anatomical structure 90 within the patient's body.Thus, the resulting circuit may include an electrical path through thepatient's body from the electric pad 123 to the valve elements 130.

The heart valve 112 may be implanted within a patient's heart, e.g., toreplace an existing natural or prosthetic valve, using known procedures,and the power source 14 may be implanted at another location, e.g.,subcutaneously, with the lead 118 a extending from the power source 14through the patient's body to the electrode 116.

The negative charge may be maintained substantially constant for anextended period of time, e.g., at a voltage between about zero (0) and−0.5 volts. For example, depending upon the life of the battery 54, thepower source 14 may maintain the negative charge constantly for the lifeof the implant, e.g., up to several decades, or may only intermittentlyapply the negative charge to the surface of the implanted device. Theimparted negative charge may repel negatively charge blood cells and/orother negatively charged cells in the blood, e.g., may inhibit theintrinsic and or extrinsic coagulation pathways to prevent blood fromcoagulating on the surfaces of the valve elements 130, which may obviatethe need to take oral anticoagulants and/or reduce the risk ofhemorrhage.

In another embodiment, the power source 114 may be configured to imparta negative charge to a conductive layer (not shown) under an outersurface of the valve elements 130, e.g., such that the valve elements130 behave similar to a capacitor maintaining a negative charge for anindefinite period of time. Thus, the power source 14 may deliver arelatively low negative voltage at the surfaces of the valve elements130, e.g., such that a small current (e.g., between about zero and fivemilliamps per square centimeter (0-5 mA/cm2) flows at the surfaces. Thisrelatively small current may increase coagulation resistance by as muchas four hundred percent (400%).

Turning to FIGS. 3A-3B, still another embodiment of an implantablemedical apparatus 200 is shown that generally includes a vascular graft,e.g., an arteriovenous hemodialysis access graft 212, and a power source214. In addition, one or more electrode elements 216 and/or leads 218may be provided, e.g., which may be secured or otherwise coupled to theaccess graft 212, similar to the previous embodiments.

The access graft 212 generally includes a main cylindrical body 242 influid communication with graft tubes 244, 246 and access tubes 264, 266via lumen 226. The cylindrical body 242 may include any materialsuitable for implantation within the human body, such as expanded PTFE.The exterior surface of the cylindrical body 242 as well as the exteriorof the graft tubes 244, 246 may be coated with an outer conductive layer240. The outer conductive layer 240 may include a conductive material,such as the polymers or monomers described elsewhere herein. Theinterior surface of the cylindrical body 242 as well as the interior ofthe graft tubes 244, 246 and the interior of the access tubes 264, 266may also be coated with an inner conductive layer 230. The innerconductive layer 230 may also include a conductive material similar tothose described elsewhere herein.

The graft tubes 244, 246 may include fittings 272, 274 that are suitablefor securing to desired locations within a patient's body, e.g., to avein, artery, or other body lumen. The access tubes 264, 266 may includeconnectors 276, 278 suitable for securing to complimentary connectors(not shown) of a dialysis machine (not shown). The connectors 276, 278may include any type of seals or valves known to a person of ordinaryskill in the art.

One or more electrodes 216 may be provided that are coupled to the innerand/or outer conductive layers 230, 240. For example, as shown, anelectrode 216 a is coupled to the inner conductive layer 230, and anelectrode 216 b is coupled to the outer conductive layer 240.

The power source 14 generally includes a circuit 50 and a battery 52within a casing 54, similar to other embodiments described herein. Forexample, the battery 52 may be a nonrechargeable or rechargeable directcurrent source with an operating voltage in the range of about −9 voltsto +9 volts, e.g., between about −0.5 and +0.5 volts, and the circuit 50may be any number of resistive or active elements for controlling flowof electrical current from the battery 52.

The power source 14 may be electrically coupled to the electrode 216 avia a negative lead 218 and to the electrode 216 b via a positive lead219. The leads 218, 219 may include one or more wires or other conducts,similar to other embodiments described herein. For example, the powersource 14 may be coupled to the access graft 212 such that a negativecharge is imparted to the inner conductive layer 230. The impartednegative charge may repel negatively charge blood cells and/or othercells and/or may inhibit the intrinsic and/or extrinsic coagulationpathways, e.g., to reduce the risk of thrombosis within the implantableaccess graft 212. In an opposite manner, the power source 14 may becoupled to the access graft 212 such that a positive charge is impartedto the outer conductive layer 240. The imparted positive charge maypreferentially increase coagulation and/or smooth muscle cellproliferation to the outer surface, which may improve sealing and/orscarring of the implantable access graft 212 in position. Alternatively,the power source 14 may be configured to apply a positive charge to thecasing 54 d outer surface, which may impart a positive charge to theouter conductive layer 240 via electrical flow through the patient'sbody.

Turning to FIGS. 4A-4B, yet another embodiment of an implantable medicalapparatus 300 is shown that generally includes a vascular graft in theform of an implantable blind-ended graft member 312 and a power source14. In addition, electrodes 316 a, 316 b may also be provided, which arecoupled to the graft member 312. The graft member 312 may beelectrically coupled to the power source 14 via a negative lead 318 anda positive lead 319.

The blind-ended graft member 312 may include an elongate tubular member320 having a proximal end 322 and a distal end 324, with a graft fitting374 attached to the distal end 324, and a septum 328 on the proximal end322. As best seen in FIG. 4B, the graft member 312 may also include aconductive layer 330 on an inner surface thereof, e.g., coupled to theelectrodes 316 a, 316 b.

The tubular member 320 may be formed from one or more materials suitablefor implantation within a patient's body, such as expanded PTFE orsilicone dispersion integrated with silver particles, carbon particles,or other electrically conductive material similar to other embodimentsdescribed herein. The graft fitting 374 may be formed from suitablematerial for securing to the vasculature of a patient using knownmethods, such as suturing. In an alternative embodiment, the graftfitting 374 may include an outer conductive layer (not shown) that is inelectrical communication with the inner conductive layer 330. A negativecharge may then be imparted to the outer conductive layer (not shown)when a negative charge is imparted to the inner conductive layer 330,e.g., as describe below.

The inner conductive layer 330 may include a polymer, such asPoly(3,4-Ethylenedioxythiophene)/poly(styrenesulfonate) or a monomersuch as 3,4-Ethylenedioxythiophene, which may be polymerized by addingFerric Toluene Sulfonate as an oxidant. In another embodiment, the innerconductive layer 330 may include a relatively thin layer of a siliconedispersion loaded with conductive particles (not shown), e.g., asdescribed elsewhere herein.

The electrodes 316 a, 316 b may be coupled to the inner conductive layer330, e.g., at proximal and distal ends 322, 324 of the tubular member320. The septum 328 may include any suitable material that is resilientand self sealing, e.g., that may be punctured with a needle aautomatically reseal upon removal of the needle.

The power source 14 may be coupled to the graft member 312 such that anegative charge is imparted to the inner conductive layer 330. Theimparted negative charge may act to repel negatively charge blood cellsand other cells from the inner lumen of the graft member 312 and/orreduce thrombosis therein by inhibiting the intrinsic and/or extrinsiccoagulation pathways.

During use, as shown in FIG. 4C, a pair of apparatus 300 a, 300 b (eachsimilar to apparatus 300 of FIGS. 4A and 4B) may be implanted within apatient's body. For example, apparatus 300 a may be implanted, e.g., bysewing into an artery 396, and apparatus 300 b may be implanted, e.g.,by sewing into a vein 398. The apparatus 300 a, 300 b may preclude bloodflow at all times except during hemodialysis, i.e., when needles,cannulas, or other devices are used to penetrate the septums 328. Thus,blood flow with a hemodialysis machine or other device (not shown) maybe established via the apparatus 300 a, 300 b by accessing each graftmember 312 a, 312 b via septum 328 a, 328 b.

Turning to FIG. 5, still another embodiment of an implantable medicalapparatus 400 is shown that generally includes an implantable dialysiscatheter 412 and a power source 14. In addition, an electrode 416 may beprovided, which may be coupled to the dialysis catheter 412, and thedialysis catheter 412 may be coupled to the power source 14 via anegative lead 418. The apparatus 400 may also include a positive lead419 attached to an electric pad 423, e.g., similar to other embodimentsdescribed herein.

The dialysis catheter 412 generally includes an elongate tubular member420 including a proximal end 422 and a distal end 424, and ahemodialysis connection assembly 470. The tubular member 420 may alsoinclude a plurality of inlet ports 482, e.g., on the distal end 424. Thetubular member 420 may be formed from a substantially flexible orsemi-rigid material, such as expanded PTFE, and a substantial portion ofan outer surface of the tubular member 420 may be coated with an atleast partially electrically conductive layer 440, similar to otherembodiments described herein.

The hemodialysis connection assembly 470 generally may include a pair ofaccess stems 474, as well as a pair of flow clamps 476 and a pair ofdialysis connectors 478. The construction of the connection assembly 470is with any number of materials and methods known to a person ofordinary skill in the art.

The power source 14 is similar to those described elsewhere herein,e.g., including a battery or other energy source, and/or one or morecircuits (not shown) for controlling electrical flow from the battery.The power source 14 may be coupled to the dialysis catheter via lead 418and to an electric pad 423 coupled to an anatomical structure within thepatient's body. The power source 14 may be configured to impart anegative charge to the conductive outer layer 440, e.g., at asubstantially constant voltage between about zero (0) and −0.5 volts.Alternatively, if the outer surface of the tubular member 420 includes aconductor, the power source 14 may be configured to deliver a lownegative voltage at the outer surface such that a small current,approximately between about zero and five (0-5) 5.0 milliamps/cm2, flowsat the surface. In another alternative, the negative charge may beimparted to the surface of the tubular member 420 by using anelectrically polarized conductor (not shown) disposed below the surfaceof the tubular member 420 instead of coating the elongate cylinder 420with the conductive outer layer 440, similar to other embodimentsdescribed herein.

FIG. 5 shows the dialysis catheter 412 being used as a “subclavian line”because of the catheters 412 anatomical location in the subclavianartery. It may be appreciated that the catheter 412 may be easilymodified for use as a “femoral line,” as a peritoneal dialysis catheter,or in other locations within a patient's body.

Turning to FIG. 6, another embodiment of an implantable medicalapparatus 500 is shown that generally includes an implantableendovascular aortic aneurysm graft 512 and a power source 14. Inaddition, electrodes 516 a, 516 b may also be provided, which arecoupled to the aortic graft 512. The aortic graft 512 may be coupled tothe power source 514 via a negative and a positive lead 518, 519 andelectrodes 516 a, 516 b, respectively.

The aortic graft 512 generally includes a main body or tubular member520 integrated with a first branch member 560 and second branch member562. The aortic graft 512 further includes a proximal stent 572 on themain body 520 and a first and second distal stent 574, 576 on the firstand second branch members 560, 562, respectively. The aortic graft 512may also include a plurality of electric conductors 578 facilitating anelectrical connection between the proximal stent 572 and the first andsecond distal stent 574, 576.

The aortic graft 512 may be formed from any number of materials suitablefor implantation and/or providing desired strength and/or durability. Inone embodiment, the aortic graft 512 may be formed from a woven orfabric material, such as nylon, polypropylene, or other polymer, orexpanded PTFE or other extruded polymers.

Optionally, the main body 520 may include an outer conductive layer 540including an at least partially electrically conductive material,similar to those described elsewhere herein. The outer conductive layer540 may facilitate improvement of an electrically charged area adjacentthe proximal stent 572. The electrode 516 b may be attached to the outerconductive layer 540, or, alternatively, may be attached to the proximalstent 572. The electrode 516 a may be coupled to the outer surface ofthe main body 520, or, alternatively, to an electric pad (not shown)coupled to an anatomical structure within the patient's body, such as asegment of the patient's vasculature, to complete the circuit.

The proximal stent 572 and the first and second distal stent 574, 576may be formed from suitable materials, e.g., to provide self-expandingor balloon-expandable stents, e.g., such that the aortic graft 512 maybe implanted using one or more catheters (not shown). If the stentmaterial is not inherently electrically conductive, the outer surface ofthe stent material may be coated with a suitable conductive material,similar to the embodiments described elsewhere herein.

The power source 14, which may be similar to those described elsewhereherein, may be coupled to the aortic graft 512 such that a positivecharge is imparted to the outer conductive layer 540, the proximal stent572, and/or the first and second distal stents 574, 576. The positivecharge may be maintained substantially constant, e.g., between aboutzero (0) and +0.5 volts. The imparted positive charge may increasethrombosis or smooth muscle proliferation particularly surround theproximal stent 572, which is a common failure site for aortic repairs.Thus, the apparatus 500 may substantially reduce the risk of endoleaksthat may otherwise occur after implantation.

Turning to FIG. 7, a flowchart 600 is shown that illustrates anexemplary method for delivering an implantable device within a body toprevent thrombosis, infection, and/or undesired tissue growth. Althoughthe steps are described in an exemplary order, it will be appreciatedthat the order of the steps may be modified and/or one or more of thesteps may be omitted. At step 610, a device may be implanted within apatient's body, the device including an at least partially electricallyconductive portion. For example, as described above, the device mayinclude a vascular graft, a prosthetic heart valve, a hemodialysiscatheter, and the like, which may be implanted within or coupled to thepatient's vasculature or other location.

At step 612, a power source may be implanted within the patient's body.For example, the power source may be implanted subcutaneously, e.g., bycreating an incision and implanting the power source beneath thepatient's skin at an accessible location. At step 614, the power sourcemay be coupled to the device, e.g., by connecting one or more leadsbetween the power source and the device. Optionally, this may includecoupling the power source to an anatomical location within the patient'sbody, e.g., thereby using the patient's body to complete a circuitbetween the power source and the device. At step 616, a negativeelectrical charge may be applied to the at least partially electricallyconductive portion, e.g., for an indefinite time to prevent thrombosis,infection, and/or undesired tissue growth, for example by resistingcells from adhering to the at least partially conductive portion.

The power source, e.g., including a battery or other energy source maybe configured to maintain a substantially constant electric charge tothe at least partially electrically conductive portion, e.g., betweenabout zero (0) and −0.5 volts, for an indefinite period of time. Forexample, when the power source has depleted, it may be replaced, e.g.,by reaccessing the subcutaneous location and replacing the battery.Alternatively, the power source may be recharged, e.g., using anexternal device that may communicate with the power source usingwireless telemetry, as described above. The power source may remain onsubstantially continuously, or may periodically turn on for apredetermined time, depending upon the application and the desiredreduction in cell adhesion.

It will be appreciated that elements or components shown with anyembodiment herein are exemplary for the specific embodiment and may beused on or in combination with other embodiments disclosed herein.

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the scope ofthe appended claims.

I claim:
 1. A method for preventing thrombosis on an implantable devicein a body, the method comprising: implanting the device within apatient's body, the device comprising an at least partially electricallyconductive portion, and a power source coupled to the at least partiallyelectrically conductive portion; and applying a negative electricalcharge to the at least partially electrically conductive portion for thelife of the device to prevent thrombosis adjacent the at least partiallyelectrically conductive portion, wherein the power source is configuredto maintain a substantially constant negative electric charge to the atleast partially electrically conductive portion that is between 0 and−0.5 volts.
 2. The method of claim 1, wherein implanting the devicecomprises: implanting an implant comprising the at least partiallyelectrically conductive portion at a first location within the patient'sbody; implanting the power source at a second location within thepatient's body; and coupling the power source to the implant.
 3. Themethod of claim 2, wherein the power source is implanted subcutaneously.4. The method of claim 2, wherein the implant is secured to vasculatureof the patient's body.
 5. The method of claim 2, wherein the implantcomprises a tubular graft, and wherein the tubular graft is securedwithin a body lumen of the patient's body.
 6. A method for preventingthrombosis on an implantable device in a body, the method comprising:implanting the device within a patient's body, the device comprising anat least partially electrically conductive portion, and a power sourcecoupled to the at least partially electrically conductive portion; andapplying a negative electrical charge to the at least partiallyelectrically conductive portion for the life of the device to preventthrombosis adjacent the at least partially electrically conductiveportion; wherein implanting the device comprises: implanting an implantcomprising the at least partially electrically conductive portion at afirst location within the patient's body; implanting the power source ata second location within the patient's body; and coupling the powersource to the implant, wherein the implant is coupled to a negativeterminal of the power source, and wherein a positive terminal of thepower source is coupled to the patient's body such that the resultingcircuit includes a portion of the patient's body.
 7. A method forpreventing thrombosis on an implantable device in a body, the methodcomprising: implanting the device within a patient's body, the devicecomprising an at least partially electrically conductive portion, and apower source coupled to the at least partially electrically conductiveportion; and delivering a small DC electric current to the at leastpartially electrically conductive portion substantially continuously tomaintain a negative charge to prevent thrombosis adjacent the at leastpartially electrically conductive portion for the life of the device. 8.The method of claim 7, wherein the power source comprises a battery anda circuit for controlling the substantially continuous flow of the smallDC current from the battery to the at least partially conductiveportion.
 9. The method of claim 7, wherein the device comprises avascular graft.
 10. The method of claim 7, wherein the device comprisesa tubular member comprising proximal and distal ends.
 11. The method ofclaim 10, wherein the power source is coupled to the tubular member tocreate a negative charge on an internal surface and a positive charge onan external surface of the tubular member.
 12. The method of claim 7,wherein the power source delivers a voltage such that the small currentis greater than zero and not more than five milliamps/cm2.
 13. A methodfor preventing thrombosis on a vascular graft, comprising: implantingthe vascular graft within a patient's body, the vascular graftcomprising a tubular member comprising a luminal surface, at least aportion of the luminal surface being electrically conductive, and apower source coupled to the luminal surface such that a small currentflows from the power source to the luminal surface, thereby maintaininga desired voltage on the luminal surface for the life of the tubularmember to prevent thrombosis.
 14. The method of claim 13, wherein thetubular member is secured within a body lumen of the patient's body. 15.The method of claim 13, wherein the power source is coupled to thetubular member to create a negative charge on the luminal surface and apositive charge on an external surface of the tubular member.
 16. Themethod of claim 13, wherein the power source delivers a voltage suchthat the small current is greater than zero and not more than fivemilliamps/cm2.